Project Summary/Abstract: Menisci are fibrocartilagenous structures that aid in load distribution and joint lubrication. Their functionality relies in part on the uniquely graded interfaces that join the menisci to the underlying bone. The microstructure of these interfaces is a testament to their efficacy as they mitigate stresses developed in the joint during every day activity; however, slow degradation of these interfaces over time may be facilitating the propagation of osteoarthritis. It is hypothesized that as we age there becomes an increased material property disparity in the attachment sites undermining the ability of menisci to attenuate loading, leading to excessive meniscal extrusion and increased wear on the joint. Current literature fails to define how the biochemical and morphological construct of the meniscal attachments transition from fibrocartilage to the underlying subchondral bone. The aims of this research plan will bridge a gap in the understanding of the mechanical environment that these interfaces must endure and how this has led to their structural development. This work is directly translatable to developing engineered replacements for diseased tissue as current strategies remain fixated on the meniscal body, despite their effectiveness relying on the need for a bio-mimetic fixation strategy. The first aim of this study is to determine the mechanical environment within meniscal attachments as a function of age. The internal fluid pressures in meniscal attachments during physiological and pathological loading of healthy, ACL transected/partially menisectomized, and aged osteoarthritic knees will be measured. Knee joints will be dynamically compressed up to 21/2X body weight, in accordance with physiological load/flexion angle data, while measuring fluid pressures in the attachments in situ, using novel fibre-optic pressure microsensors. The second aim is to quantify the material properties and degree of mineralization at the transition zone as a function of age, including healthy and osteoarthritic meniscal attachments. Meniscal attachments will be excised from the dynamically tested knee joints. The material properties will be determined for the transition zones of human meniscal attachments using a nanoindenter. Calcification will be determined using quantitative backscattered electron microscopy. These data will be statistically compared to elucidate differences between zones and anatomical location as a function of age. Osteoarthritis symptoms can develop as young as 40 years old, however, its prevalence increases to 50% among adults over 65. Limited joint functionality as a result of this disease is a major cause of work disability and reduced quality of life. Elderly individuals reduced to non-ambulatory states are imperiled to greater risks of life threatening conditions such as heart disease and diabetes. This research will potentially revolutionize the care of our elderly and lay the groundwork to develop preventative techniques for potential at risk patients, young and old, as well as tissue engineered replacements for those already suffering with osteoarthritis. This project strives to characterize a complex biological structure, determine a root mean cause for an age-related disease, and disseminate the findings amongst peers. To accomplish these aims training is required across scientific, technical, and communication fields of study. Explicitly, the goals of the training plan entail developing proficiency with cutting edge biological research tools including pressure microsensors, scanning electron microscopy, and nanoindentation, by means of substantive collaboration with leading research scientists. Competency, relevance, and progression will regularly be evaluated by a diverse scientific audience spanning mechanical, biological, and medical disciplines. This endeavor will not only afford an opportunity to bolster the state of the art but also serve to induct and accelerate another mind into the field of age-related research.